The goal of this project is to develop low cost portable flow cytometers for use in biomedical applications. Such instruments would have a large impact in many areas including medicine (HIV and cancer diagnosis), homeland defense (biological point detection, bio-surveillance, and forensic analysis) and general biomedical research (ligand-receptor studies, molecular assembly analysis, high throughput screening and genotyping). The many powerful applications have made flow cytometers a fixture in nearly every university, medical school, pharmaceutical company, and diagnostic lab. However, the size, expense and requirement for large amounts of consumables have limited their use to formal laboratory settings. A low cost portable flow cytometer would make these applications available to all clinicians and researchers, which would have a great impact on world health and research. To develop such an instrument we will develop (in the R21 phase) technologies that allow particle focusing without the use of sheath fluid. The elimination of sheath fluid will result in increased portability of the instrument and also reduce consumable requirements. Our novel technology will allow a sheathless portable flow cytometer to achieve conventional particle analysis rates, while using a fraction of the power and consumables of a conventional flow cytometer. We will also develop low power excitation/detection systems (R21 phase) that will not require extensive thermoregulation to achieve optical measurement stability. Such systems will significantly reduce the size, cost and power requirements of a flow cytometer. Finally, we will integrate the above technologies into a miniature affordable flow cytometer, with advanced sample handling capabilities that has significantly reduced consumable and power requirements (R33 phase). To do this we will combine the above technologies into a microfabricated flow cytometer core that can easily be interfaced with sample handling and optical modules. We will also develop a miniature low power data acquisition system to enable assembly of a complete miniature low power flow cytometer. We will validate instrument performance using quantitative flow cytometry techniques.